Method for producing cyclohexadecanone

ABSTRACT

The invention relates to a process for the production of cyclohexadecanone by hydrogenation of cyclohexadecenone and odoriferous substance mixtures, as well as products containing the cyclohexadecanone according to the invention.

The present invention relates to a process for the production ofcyclohexadecanone by hydrogenation of cyclohexadecenone and odoriferoussubstance (fragrance) mixtures as well as products containing thecyclohexadecanone according to the invention.

Macrocyclic ketones with 14-membered to 18-membered rings are generallyknown as musk fragrances. Cyclohexadecanone is contained for example inglandular secretions of some types of civet cats (K. Bauer, A. Garbe, H.Surburg, Common Fragrance and Flavor Materials, p. 169, Wiley-VCH,Weinheim, 1997).

Cyclohexadecanone can be produced according to DE-A 2 111 753 byhydrogenation of 8-cyclohexadecenone. In the hydrogenation describedthere, very large amounts of hydrogenation catalysts are employed.

In EP-A 1 201 738 cyclohexadecanone is produced by hydrogenation of8-cyclohexadecenone on palladium in ethanol. The weight ratio ofpalladium to cyclohexadecenone was 1:603, and the yield was about 76% oftheory.

In Chemistry Letters, 1973, 667-670, cyclohexadecanone was produced from5-cyclohexadecenone by means of hydrogenation. No reaction conditionsare given. There is therefore a need to find a process that yieldscyclohexadecanone economically and in good perfumery quality, inparticular on an industrial scale. The present invention provides aprocess for the production of cyclohexadecanone by hydrogenation ofcyclohexadecenone in the presence of metallic palladium, characterisedin that the weight ratio of palladium to cyclohexadecenone is below1:5000.

The present invention also provides solutions, odoriferous substancemixtures and products, preferably perfumed products, containing thecyclohexadecanone produced according to the invention.

For the process according to the invention the weight ratio of palladiumto cyclohexadecenone is below 1:5000, advantageously in the range from1:8000 to 1:5,000,000, preferably in the range 1:12,000 to 1:2,000,000,particularly preferably in the range 1:20,000 to 1:800,000 and mostparticularly preferably in the range from 1:25,000 to 1:500,000.

The amount of palladium refers in this connection to the absolutecontent of palladium, i.e. without carrier material and without thepossible presence of water or diluents.

Cyclohexadecenones within the meaning of the invention may contain 1 to3 olefinic double bonds, cyclohexadecenones with 1 olefinic double bondbeing preferred.

According to the invention (E)- or (Z)-cyclohexadecenone and arbitrarymixtures of these (E)- or (Z)-isomers may be used. According to theinvention all regioisomeric cyclohexadecenones and arbitrary mixtures ofthese compounds may be used. It is preferred to use 5-cyclohexadecenoneand 8-cyclohexadecenone, particularly preferred being8-cyclohexadecenone, wherein an (E):(Z) ratio of 1:10 to 10:1 ispreferred, a ratio of 1:5 to 5:1 is particularly preferred and a ratioof 1:3 to 4:1 is most particularly preferred. In a particularlyadvantageous modification 8-cyclohexadecenone is used with an (E):(Z)ratio of 1:1 to 3:1.

Cyclohexadecenones and processes for their production are described forexample in J. Org. Chem. 1971, 36, 3266-3270; J. Org. Chem. 1971, 36,4124-4125; Tetrahedron Lett. 1965, 21, 1537-1540 or also in Bull. Chem.Soc. Jpn. 1980, 53, 2958-2961.

The cyclohexadecenones used in the process according to the inventionpreferably have a good odoriferous quality, i.e. the cyclohexadecenonesthat are employed do not contain any chemically and odoriferouslysignificant interfering impurities. The chemical purity ispreferably >96 wt.%, particularly preferably >98 wt.%.

The palladium may for example be used in finely divided form, applied tocarriers or together with other metals (e.g. mixtures, alloys). Thecatalysts may be doped with one or more arbitrary metals.

The palladium may be applied to organic or inorganic carrier materials.The catalysts may contain a carrier material or mixtures of carriermaterials. As advantageous carrier materials there may be mentionedactivated charcoal, charcoal, aluminium oxides, metal oxides, silicagels, zeolites, clays, granulated clays, amorphous aluminium silicates,or other inorganic carriers. A preferred carrier material is activatedcharcoal.

A particularly preferred catalyst is palladium on activated charcoal.

If catalysts containing carrier materials are employed, then the amountof palladium on the carrier material is generally 0.5 to 50 wt.%,preferably 1 to 20 wt.%, particularly preferably 3 to 10 wt.% and mostparticularly preferably 4 to 7 wt.%, referred to the dry catalyst.

For the process according to the invention the catalyst may be used inthe dry or wet state (residual moisture consisting of water).

It is also possible to produce the palladium metal in situ before thestart of or during the hydrogenation by reduction with hydrogen fromcorresponding compounds such as oxides or salts, in which the palladiummay optionally be deposited on a carrier. Suitable for this purpose arefor example palladium halides such as palladium(II) chloride.

The process according to the invention may be carried out using diluentsor mixtures of diluents. Diluents that are inert under the employedhydrogenation conditions are suitable, such as for example monohydric orpolyhydric alcohols, aqueous mixtures containing monohydric orpolyhydric alcohols, ketones, ethers, esters, aromatic or saturatedhydrocarbons. Preferred are alcohols with 1 to 4 carbon atoms, alkaneswith 5 to 15 carbon atoms, ketones with 3 to 8 carbon atoms, open-chainor cyclic ethers with 4 to 10 carbon atoms, esters with 3 to 12 carbonatoms or aromatic hydrocarbons with 6 to 10 carbon atoms. There maytypically be used diluents such as methanol, ethanol, isopropanol,n-propanol, isobutanol, n-butanol, sec.-butanol, tetrahydrofuran,dibutyl ether, ethylene glycol dimethyl ether, acetone, butanone,2-pentanone, 3-pentanone, hexanone, cyclohexanone, methyl ethyl ketone,diethyl ketone, diisopropyl ketone, methyl isobutyl ketone, ethylacetate, methyl acetate, n-pentane, n-hexane, n-heptane, n-octane,isooctane, cyclopentane, cyclohexane, methylcyclohexane, cyclooctane,benzene, toluene, ethylbenzene, xylenes; preferred are ethanol,isopropanol, acetone, methyl ethyl ketone and toluene.

Also preferred are diluents that are acceptable as regards perfumery,dermatological or cosmetic criteria. Such diluents are preferablyethanol, dipropyiene glycol, propylene glycol, 1,2-butylene glycol,glycerol, diethylene glycol monoethyl ether, diethyl phthalate,isopropyl myristate, triethyl citrate; benzyl benzoate and benzylacetate. Particularly preferred are ethanol, diethyl phthalate,propylene glycol, dipropylene glycol, triethyl citrate and isopropylmyristate.

The weight ratio of cyclohexadecenone and diluent is advantageously inthe range from 1:10 to 4:1, preferably, in the range from 1:5 to 3:1,particularly preferably in the range from 1:2 to 2:1. In a preferredembodiment the proportion of cyclohexadecenone is 40 to 80 wt.%,particularly preferably 45 to 75 wt. %, referred. to the mixture ofcyclohexadecenone and diluent.

The hydrogenation may be carried out in the presence of diluents attemperatures of 0° to 150° C. Advantageously temperatures in the rangefrom 10° to 100° C., preferably in the range from 20° to 85° C. andparticularly preferably in the range from 30° to 60° C. are employed.

The hydrogenation may also be carried out in the absence of diluents attemperatures above 60° C., preferably in the range from 70° to 150° C.,particularly preferably at 70° to 100° C. A high and/or excessively longthermal stress has a deleterious effect on the odoriferous quality ofthe cyclohexadecanone. After the hydrogenation in the absence ofdiluents a purification step is preferably carried out, which preferablycomprises a recrystallisation.

According to the invention the hydrogenations are carried out withelementary hydrogen.

The hydrogen pressure is suitably 1 to 100 bar, preferably 1 to 30 bar,particularly preferably 3 to 20 bar and most particularly preferably 5to 15 bar.

The reaction time of the hydrogenation is preferably 2 to 80 hours,particularly preferably 5 to 40 hours and most particularly preferably 8to 25 hours.

Following the hydrogenation it may be advantageous, particularly asregards the odoriferous quality, to carry out a recrystallisation afterseparating the catalyst.

The recrystallisation is particularly advantageously carried out usingalcohols with 1 to 8 carbon atoms, alkanes with 5 to 15 carbon atoms,ketones with 3 to 8 carbon atoms, open-chain or cyclic ethers with 4 to10 carbon atoms, esters with 3 to 12 carbon atoms or aromatichydrocarbons with 6 to 10 carbon atoms. Preferred are methanol, ethanol,isopropanol, n-propanol, isobutanol, n-butanol, sec.-butanol,tetrahydrofuran, dibutyl ether, ethylene glycol dimethyl ether, acetone,butanone, 2-pentanone, 3-pentanone, hexanone, cyclohexanone, methylisobutyl ketone, ethyl acetate, methyl acetate, n-pentane, n-hexane,n-heptane, n-octane, isooctane, cyclopentane, cyclohexane,methylcyclohexane, cyclooctane, benzene, toluene, ethylbenzene, xylenes;particularly preferred are methanol, ethanol, acetone, isopropanol, andtoluene.

In a particularly advantageous embodiment the thermal treatment duringthe overall process, i.e. the hydrogenation and the optionallysubsequent purification (e.g. crystallisation or distillation) iscarried out at temperatures of less than or equal to 150° C., preferablyat temperatures less than or equal to 130° C. and particularlypreferably at temperatures less than or equal to 100° C.

The cyclohexadecanone produced according to the invention is a verycomplex musk compound and has a valuable odoriferous spectrum. Inperfumery terms cyclohexadecanone manifests marked similarities tomuscone and cyclopentadecanone as well as a strong macromusk note, andin addition to this cyclohexadecanone is characterised by the pronounced“animal” note of musk tincture or natural tonkin musk. Furtherodoriferously interesting aspects are ambrette and nitromusk, with acertain accompanying fruitiness.

The cyclohexadecanone produced according to the invention alreadypossesses as hydrogenation crude product, especially if thehydrogenation is carried out in the presence of diluents, a goodperfumery quality. Hydrogenation crude product is understood to denotethe product derived directly from the hydrogenation, after removal ofthe hydrogenation catalyst. The hydrogenation crude product may forexample be present as immediate solution in the diluent used in thehydrogenation, enriched in this by partial removal of the diluent, orobtained as pure substance after removal of the diluent.

If the hydrogenation crude product is to be used as solution or is to beprocessed further, then it is advantageous to carry out thehydrogenation in the presence of a diluent that is acceptable forperfumery, dermatological or cosmetic use, so that the solutioncontaining the hydrogenation crude product can be employed as such. Thehydrogenation crude product according to the invention may be used, inparticular as a solution in the diluent in the presence of which thehydrogenation was carried out, without further purification steps as anodoriferous substance, in perfumery compositions and for imparting apleasant smell.

The process according to the invention may for example be carried out asfollows:

Cyclohexadecenone and the catalyst and optionally a diluent are placedin a pressurised vessel equipped with a stirrer. Hydrogenation iscarried out at the chosen reaction temperature and hydrogen pressure.The hydrogenation crude product is typically obtained after removal ofthe catalyst by filtration, decanting or centrifugation. In the case ofa diluent-free hydrogenation the separation of the catalyst must becarried out at elevated temperature, which advantageously is above themelting point of the cyclohexadecanone. A more comprehensivepurification may optionally be carried out, for example by distillation,crystallisation or steam treatment. The cyclohexadecanone can beobtained in an almost quantitative yield (generally greater than 97wt.%) by the process according to the invention.

Cyclohexadecanone can be produced in a high state of purity and in verygood yield by the process according to the invention. The processaccording to the invention is therefore particularly advantageous fromeconomic, technical and industrial aspects.

The cyclohexadecanone produced by the process according to the inventionmay in particular be used as an odoriferous substance, in perfumerycompositions, perfumery oils, odoriferous substance mixtures or aromacompositions.

Odoriferous substances with which cyclohexadecanone may be combined aredescribed for example in Bauer, Garbe, Surburg, Common Fragrance andFlavor Materials, Wiley-VCH, 4^(th) Edition, 2001.

A further area of application of cyclohexadecanone or of odoriferoussubstance mixtures containing cyclohexadecanone are perfumed products,preferably hygiene or body care products, especially in the householdand body care sector.

Cyclohexadecanone is characterised in particular by a good adsorption onsynthetic and natural fibres, hair, as well as the skin.

The perfumery oils containing the cyclohexadecanone produced accordingto the invention may be used in concentrated form, in solutions or inanother modified form for the production of, for example, perfumeextracts, eau de parfums, eau de toilettes, aftershave lotions, eau decolognes, pre-shave products, splash colognes and perfumed freshenerwipes as well as the perfuming of acidic, alkaline and neutral cleaningagents such as e.g. floor-cleaning agents, window-cleaning agents,washing-up liquids and dishwasher formulations, bath and sanitarywarecleaning agents., scouring agents, solid and liquid WC-cleaning agents,powder-type and foam-type carpet-cleaners, liquid detergents,pulverulent detergents, wash pretreatment agents such as bleachingagents, soaking agents and stain-removers, textile softeners, washingsoaps, washing tablets, disinfectants, surface disinfectants as well asair-fresheners in liquid or gel-like form or applied to a solid carrier,aerosol sprays, waxes and polishes such as furniture polishes, floorwaxes, shoe creams as well as body care agents, such as for examplesolid and liquid soaps, shower gels, shampoos, shaving soaps, shavingfoams, bath oils, cosmetic emulsions of the oil-in-water, water-in-oiland water-in-oil-in-water type, such as e.g. skin creams and lotions,face creams and lotions, sunscreens and lotions, after-sun creams andlotions, hand creams and lotions, foot creams and lotions, depilationcreams and lotions, aftershave creams and lotions, tanning creams andlotions, hair care products such as e.g. hairsprays, hair gels, hairlotions, hair rinses, permanent and semi-permanent hair dyes,hair-shaping means such as cold waves and hair smoothing agents, hairtonics, hair creams and lotions, deodorants and antiperspirants such ase.g. underarm sprays, roll-ons, deodorant sticks, deodorant creams ordecorative cosmetics products.

The following examples illustrate the invention.

EXAMPLE 1

In Example 1 the ratio of Pd:8-cyclohexadecenone is about 1:18,520.

100 kg of 8-cyclohexadecenone (odoriferously good quality; the gaschromatography (GC) ratio of (E) and (Z) isomers was 3:1) and 180 g ofpalladium on activated charcoal (Pd content: 5 wt. %) with 40% watercontent were placed in a stirred autoclave equipped with a gassingstirrer. The reaction mixture was hydrogenated for 17 hours at 75° C.and 20 bar hydrogen pressure and then filtered at about 75° C. The yieldof hydrogenation crude product was >98% (GC content ofcyclohexadecanone: >97%). The perfumery quality could be improved stillfurther by recrystallisation from methanol or by steam treatment.

EXAMPLE 2

In Example 2 the ratio of Pd:8-cyclohexadecenone is about 1:7,500.

180 kg of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers: 65:34) in 180 kg of diethyl phthalate and 800 g ofpalladium on activated charcoal (Pd content: 5 wt. %) with 40% watercontent were placed in a stirred autoclave equipped with a gassingstirrer. The reaction mixture was hydrogenated for 20 hours at 49° to52° C. and 5 bar hydrogen pressure. After filtration 349 kg ofcyclohexadecanone were obtained as 50% solution in diethyl phthalate.The yield of cyclohexadecanone in terms of conversion was >99%. Theproduct thereby obtained was of a good perfumery quality.

EXAMPLE 3

In Example 3 the ratio of Pd:8-cyclohexadecenone is about 1:15,000.

180 kg of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers: 64:34.5) in 180 kg of isopropyl myristate and 400 gof palladium on activated charcoal (Pd content: 5 wt. %) with 40% watercontent were placed in a stirred autoclave equipped with a gassingstirrer. The reaction mixture was hydrogenated for 40 hours at 4 to 5bar hydrogen pressure, in which connection the temperature was raisedduring the course of the hydrogenation from the initial value of 50° C.to 125° C. After filtration 346 kg of cyclohexadecanone were obtained as50% solution in isopropyl myristate. The yield of cyclohexadecanone interms of conversion was >99%. The product thereby obtained was of a goodperfumery quality.

EXAMPLE 4

In Example 4 the ratio of Pd:8-cyclohexadecenone is about 1:33,333.

100 kg of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers was 2.5:1), 45 kg of acetone and 100 g of palladiumon activated charcoal (Pd content: 5 wt. %) with 40% water content wereplaced in a stirred autoclave equipped with a gassing stirrer. Thereaction mixture was hydrogenated for 12 hours at 35° to 40° C. and at15 bar hydrogen pressure and then filtered. After removing the acetone99.2 kg of cyclohexadecanone were obtained (GC content ofcyclohexadecanone: >98%). The product thereby obtained was of a goodperfumery quality. The perfumery quality could be improved still furtherby recrystallisation from methanol.

EXAMPLE 5

In Example 5 the ratio of Pd:8-cyclohexadecenone is about 1:5,556.

1000 kg of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers was 2:1) in 1000 kg of ethanol and 6 kg of palladiumon activated charcoal (Pd content: 5 wt. %) with 40% water content wereplaced in a stirred autoclave equipped with a gassing stirrer. Thereaction mixture was hydrogenated for 18 hours at 30° to 50° C. and 6bar hydrogen pressure. After filtration 2002 kg of a 50% solution ofcyclohexadecanone in ethanol (GC purity without ethanol >97%) wereobtained. The yield of cyclohexadecanone was >99%. The product therebyobtained was of a good perfumery quality. The perfumery quality could beimproved still further by recrystallisation from ethanol.

EXAMPLE 6

In Example 6 the ratio of Pd:8-cyclohexadecenone is about 1:7,778.

700 g of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers was 63.4:35.5), 300 g of acetone and 3 g ofpalladium on activated charcoal (Pd content: 5 wt. %) with 40% watercontent were placed in a stirred autoclave equipped with a gassingstirrer. The reaction mixture was hydrogenated for 8 hours at 55° to 60°C. and 5 bar hydrogen pressure. 992 g of hydrogenation crude productwere obtained, and the GC purity of the cyclohexadecanone was 99.4% (theacetone was disregarded). The product thereby obtained was of a goodperfumery quality.

EXAMPLE 7

In Example 7 the ratio of Pd:8-cyclohexadecenone is about 1:6,667.

800 g of 8-cyclohexadecenone (odoriferously good quality: ratio of (E)and (Z) isomers was 1.8:1), 400 g of acetone and 4 g of palladium onactivated charcoal (Pd content: 5 wt. %) with 40% hydrogen content wereplaced in a stirred autoclave equipped with a gassing stirrer. Thereaction mixture was hydrogenated for 8 hours at 25° C. and 18 barhydrogen pressure and then filtered. 991 g of hydrogenation crudeproduct were obtained, the GC purity of the cyclohexadecanone being99.3% (the acetone was disregarded). The product thereby obtained was ofa good perfumery quality.

EXAMPLE 8

In Example 8 the ratio of Pd:8-cyclohexadecenone is about 1:8,317.

998 g of 8-cyclohexadecenone (odoriferously good quality: GC ratio of(E) and (Z) isomers was 63.4:35.5) and 4 g of palladium on activatedcharcoal (Pd content: 5 wt. %) with 40% water content Were placed in astirred autoclave equipped with a gassing stirrer. The reaction mixturewas hydrogenated for 15 hours at 95° C. and 18 bar hydrogen pressure andthen filtered at about 95° C. The yield of hydrogenation crude productwas >98% (GC content of cyclohexadecanone was 96%). The perfumeryquality could be improved still further by recrystallisation frommethanol or by steam treatment.

1. Process for the production of cyclohexadecanone by hydrogenation ofcyclohexadecenone in the presence of a hydrogenation catalyst comprisingmetallic palladium in a weight ratio of palladium to cyclohexadecenone,characterized in that the weight ratio of palladium to cyclohexadecenoneis below 1:5,000.
 2. Process according to claim 1, characterized in thatthe weight ratio of cyclohexadecenone is in the range from 1:8,000 to1:5,000,000.
 3. Process according to claim 1, characterized in thatpalladium on activated charcoal is used as said hydrogenation catalyst.4. Process according to claim 1, characterized in that saidcyclohexadecenone comprises 8-cyclohexadecenone is used.
 5. Processaccording to claim 1, characterized in that the hydrogenation is carriedout in the presence of a diluent, and the weight ratio ofcyclohexadecenone and diluent is in the range from 1:10 to 4:1. 6.Process according to claim 1, characterized in that the hydrogenation iscarried out in the absence of a diluent at temperatures in the rangefrom 70° to 150° C.
 7. Process according to claim 1, characterized inthat the hydrogenation is carried out in a diluent that is acceptable asregards perfumery, dermatological or cosmetic criteria.
 8. Processaccording to claim 1, characterized in that the diluent comprisesethanol, isopropanol, acetone, methyl ethyl ketone, toluene, diethylphthalate, propylene glycol, dipropylene glycol, triethyl citrate and orisopropyl myristate.
 9. Process according to claim 1, characterized inthat after the hydrogenation a recrystallization is carried out. 10.Process according to claim 1, characterised characterized in that thereaction time of the hydrogenation is 2 to 80 hours.
 11. Solutionscontaining the cyclohexadecanone produced according to the process ofclaim
 1. 12. Solutions according to claim 11, wherein said hydrogenationis performed with a diluent that is acceptable as regards perfumery,dermatological or cosmetic criteria.
 13. Odoriferous substance mixturescontaining the cyclohexadecanone produced according to claim
 1. 14.Product containing the cyclohexadecanone produced according to claim 1.